Malignant carotid body tumor

CONTROVERSY

Ramon M. Esclamado, MD, Section Editor

MALIGNANT CAROTID BODY TUMOR

Consultants: William Carroll, MD1 Kerstin Stenson, MD2 Scott Stringer, MD3

1 Division of Otolaryngology, University of Alabama, Birmingham, Alabama2 Department of Otolaryngology, University of Chicago, Chicago, Illinois3 Department of Otolaryngology, University of Mississippi Medical Center, Jackson, Mississippi

CASE PRESENTATION

A 38-year-old woman initially presented with a

3-week history of decreased hearing in the left ear.

Evaluationrevealedaleftserousotitismedia,withno

evidenceofanasopharyngealmass.Shewastreated

forallergicrhinitis,withsubsequentresolutionofher

serous effusion. During the third trimester of her

subsequent pregnancy, she noted a progressive

globussensationandleft-sidedintermittentotalgia.

A CT scan after her pregnancy showed a 2- � 2-cm

enhancing mass at the left carotid bifurcation. In

addition, prominent soft tissue was noted in the

nasopharynx and tongue base, with bilateral 1-cm

level II nodes. She was subsequently referred for

furtherevaluationandmanagement.Shehadhadan

upper respiratory infection 2 weeks before the CT

scanbutnofevers,chills,ornightsweats.Shesmoked

one pack of cigarettes per day for 20 years but

otherwisewasingoodhealth.

Physical examination at the time of referral

revealed an obese, anxious woman, with a slightly

hyponasal voice. There was a left-sided serous

middle ear effusion. No trismus was present, but

prominent Waldeyer’s ring lymphoid tissue was.

Fiberoptic nasolaryngoscopy revealed prominent

nasopharyngeal lymphoid tissue abutting the left

eustachian tube orifice with purulent exudate. A

laryngeal and hypopharyngeal examination was

unremarkable. A mildly tender, 2-cm mass was

detected at the left carotid bulb, and rubbery,

mobile small lymph nodes were found at level II

bilaterally. There were no cranial nerve deficits.

Question 1: What is your differential diagnosis

at this time?

Dr. Carroll: The salient features of the history

and physical examination of this patient include:

unilateral serous otitis in a smoker, neck mass,

fullness in Waldeyer’s ring, and progression of

symptoms with pregnancy. Initial diagnostic con-

siderations includenasopharyngealororopharyng-

eal neoplasm (epithelial or lymphoid). Progression

of symptoms with pregnancy could be due to be-

nign lymphoid hyperplasia, but an estrogen recep-

tor (+) malignancy such as metastatic breast

carcinoma could also be responsible, particularly

in a 38-year-old woman.

Dr. Stenson: Nasopharyngeal carcinoma with

metastatic lymphadenopathy should be the diag-

nosis of exclusion. Other diagnoses to consider

would be lymphoma as well as infection of the

adenoid tissue secondary to her recent upper

respiratory infection. The finding of an enhanced

Department of Otolaryngology and Communicative Disorders, TheCleveland Clinic Foundation, 9500 Euclid Avenue (A71), Cleveland, Ohio44195Head & Neck 26: 301–306Published online 12 February 2004 in Wiley InterScience(www.interscience.wiley.com). DOI: 10.1002/hed.20017

B 2004 Wiley Periodicals, Inc.

Malignant Carotid Body Tumor HEAD & NECK March 2004 301

mass at the carotid bifurcation raises the diagnosis

of carotid body tumor.

Dr. Stringer: At this point, my differential diag-

nosis includes lymphoma, a carotid body tumor,

a nasopharyngeal carcinoma, oropharyngeal car-

cinoma, eustachian tube dysfunction, adenoiditis,

and chronic rhinosinusitis. However, my level of

concern for anything other than adenoiditis, eusta-

chian tube dysfunction, and a carotid body tumor is

very low given the lack of any other findings on the

CT scan. Iwould continue to consider lymphoma as

a possibility, however.

Question 2: She was treated with a 10-day

course ofAugmentin (GlaxoSmithKline,U.K.), and

re-evaluation at 2 weeks revealed resolution of the

purulent exudate and about 50% regression of the

nasopharyngeal soft tissue. Results of her neck

examination remained unchanged. What would be

your next step in evaluation?

Dr. Stenson: In terms of the nasopharyngeal

abnormality and lymphadenopathy, one should

consider performing a biopsy of the nasopharyn-

geal tissue (after evaluation for vascular anom-

aly), performing fine-needle aspiration (FNA) of

the cervical lymphadenopathy, or both. These low-

risk procedures can be done in the clinic setting.

Significant information about the diagnosis of the

nasopharyngeal abnormality and ultimate further

testing (if and when) for the carotid body tumor

can be acquired. If the index of suspicion for

malignancy were low or if biopsy and FNA as

outlined above were negative for malignancy, the

surgeon could counsel the patient about treatment

for her carotid body tumor. The surgeon would

then order a four-vessel angiogram to assess

patency of circle of Willis and cross-filling of the

cerebral hemispheres. The carotid body tumor

should then be embolized, and surgery planned

1–3 days thereafter.

Dr. Stringer: Assuming that there was no

evidence of deep infiltration in the nasopharynx

or oropharynx on the CT scan, I would proceed

with planning excision of the carotid body tumor.

My suspicion for lymphoma or a nasopharyngeal

carcinoma has become even lower given the res-

ponse to antibiotics. However, I have occasionally

observed an apparent response of malignant tu-

mors to antibiotics due to a decrease in associated

infection. Therefore, I would consider a nasopha-

ryngeal examination under anesthesia, with a

possible biopsy, depending on the status of the

serous effusion at this point. It will also be pos-

sible to access the lymphadenopathy directly at

the time of excision of the carotid body tumor.

Were it not for the lymphoid hypertrophy in Wal-

deyer’s ring, I would not be overly concerned

about bilateral, stable, 1-cm level II lymph nodes

in this patient.

Dr. Carroll: Most carotid body tumors are

strongly suspected on the basis of examination

and CT. The physical findings of carotid body

tumor are distinctive and alone raise suspicion. A

2-cm carotid body tumor is typically much more

fixed to the bifurcation and is firmer and more

pulsatile than is a metastatic node of the same

size. When coupled with typical CT findings of a

mass splaying the carotid bifurcation, the sur-

geon is alerted that the case is more than a neck

mass of unknown primary. The usual workup for

persistent neck mass of unknown primary is

staging endoscopy followed by excision node

biopsy. If carotid body tumor is not suspected

before this stage, the results can be disastrous.

The persistence of multiple small nodes and

fullness in Waldeyer’s ring following antibiotics

in this case does warrant examination under

anesthesia and biopsy to exclude concurrent

lymphoma or carcinoma.

Question 3: A bilateral carotid angiogram was

obtained (Figure 1) because the patient refused

MRI. No other vascular lesions are noted in the

head and neck, and the circle of Willis is patent.

Are any other diagnostic studies indicated?

Dr. Stringer: If the patient has a positive family

history for paragangliomas, I would counsel her in

regard to genetic testing. If possible, I would also

obtain MR images to be sure there are no other

undetected paragangliomas that would alter my

treatment planning. Without a positive family his-

tory, I believe that the CT alone is an adequate

examination. Isolated carotid body tumors are

rarely catecholamine-secreting, so, absent any

other symptoms, I would not order a urine cate-

cholamine analysis. I do not routinely order angio-

grams for diagnosis of carotid body tumors. I

obtain an angiogram only if I plan to embolize the

tumor preoperatively, and the benefit of emboliza-

tion is controversial.

Dr. Carroll: Once the diagnosis of carotid body

tumor, or anymass in the parapharyngeal space, is

entertained, we recommend MRI/MRA. The clas-

sic splaying of the internal and external carotid

arteries is usually seen clearly on MRI. Flow voids

within the tumor raise the suspicion of a para-

ganglioma. With MRA, the course or the great

vessels, the feeding vessels to the mass, and any

significant tortuosity or luminal narrowing of the

great vessels are often evident.

HEAD & NECK March 2004302 Malignant Carotid Body Tumor

Once the diagnosis of carotid body tumor is

strongly suspected, multicentric tumors need to

be excluded. MRI is an excellent screening tool

for this purpose. Carotid body tumors can be

associated concurrently with paraganglioma in

any of the head and neck sites. With this patient’s

history of middle ear disease and ear pain, the

possibility of a co-existent glomus jugulare or

glomus tympanicum should not be ignored. Most

carotid body tumors are not vasoactive (1–5%).We

typically screen, however, for elevated urine

catecholamines. Blood pressures should also be

checked, and symptoms of flushing and tachycar-

dia discussed.

The final diagnostic study that we typically ob-

tain for a carotid body tumor is a cerebral angio-

gram. This is scheduled the day before surgery so

that the tumor can be embolized if indicated. Most

tumors at our institution are embolized preoper-

atively. Small tumors with limited vascularity are

an exception.

Dr. Stenson: The treating physician should or-

der either a serum or 24-h urine studies for vanil-

lylmandelic acid (VMA) and metanephrines to

determine if the tumor is catecholamine-secreting.

Question 4: What are your indications for

preoperative test occlusion of the carotid artery?

Dr. Carroll: Balloon occlusion of the internal

carotid artery and cerebral perfusion using radio-

nuclide-enhanced SPECT are used on all pa-

tients. One of our neuroradiologists, Dr. Joe

Horton, was part of the team at Pittsburgh in

the late 1980s that demonstrated the value of this

technique for establishing safety of sacrifice of the

internal carotid artery. About 5% of patients

develop neurological symptoms in the radiology

suite with balloon occlusion alone. These patients

do not have nuclear medicine imaging and are

very high risk if the carotid artery is sacrificed or

clamped for an extended period. Of the remaining

patients, approximately 14% show a significant

focal decrease in the cerebral blood flow on

SPECT imaging. The risk of cerebrovascular

accident (CVA) is greater than 90% if carotid

sacrifice or extended clamping of the carotid is

necessary for these patients. For those patients

with minimal or no impairment of cerebral per-

fusion, the risk of CVA is 2–3% with carotid

occlusion. Symptomatic complication rates for

these studies are less than 1%. We believe this

clinical information is valuable. Given the diffi-

culty of surgical resection of these tumors and the

possibility of having to apply clamps to the carotid

arteries to gain control or replace the segment of

the artery with a graft, we believe that these

studies are justified.

Dr. Stenson: Shamblin1 describes three differ-

ent types or stages of carotid body tumors. Type I

consists of a small tumor that is easily dissected

from the adjacent vessels in a periadventitial

plane. Type II tumors are larger and more adhe-

rent and partially surround the vessel. Type III

tumors are large and completely surround the ca-

rotid bifurcation. As described, types II and III

tumors aremost likely to require carotid resection.

One should determine via CT scanning if the

tumor encases the common and/or internal carotid

artery. If there appears to be a type II or III tumor,

preparation for carotid replacement, including

test balloon occlusion with electroencephalogram

monitoring (during the test occlusion as well as

during resection) should be arranged. The subse-

quent intraoperative expertise of our vascular col-

leagues is critical for the carotid shunting and

replacement aspects of this operation.

Dr. Stringer: I no longer use any preoperative

carotid artery blood flow analysis, including pre-

FIGURE 1. Carotid angiogram.


operative test occlusion. The relationship between

this test and patient outcome in terms of stroke is

not reliable enough for planning purposes. The

size of the tumor would not affect my decision in

this regard.

Question 5: What are your treatment recom-

mendations?

Dr. Stenson: If the patient has not already had

a biopsy of the nasopharyngeal tissue, this step

should be completed. If nasopharyngeal malig-

nancy is ruled out, the patient should be prepared

for resection of her carotid body tumor. Preopera-

tive four-vessel angiogram with embolization of

the tumor should be completed at this time. Sched-

ules permitting, surgery should occur 1–3 days

thereafter to minimize post-embolic neovascular-

ization and inflammation. As a routine part of the

surgical approach, the level II and III lymph nodes

are removed via a selective neck dissection. This

not only enhances exposure but also allows for

pathologic analysis of the lymph nodes for meta-

static paraganglioma. Surgical technique involves

early identification of cranial nerves, ligation of

the external carotid artery, and meticulous peri-

adventitial dissection of the tumor from the carotid

bifurcation and internal carotid artery with liberal

use of the bipolar cautery.

Dr. Stringer: I recommend excision of the

carotid body tumor and nasopharyngeal and oro-

pharyngeal examination with possible biopsy, de-

pending on the findings. If after upper endoscopy

I noted abnormal lymph nodes upon entering the

neck, I would excise them and send one or more for

frozen section analysis in this particular case,

primarily because of the nasopharyngeal abnor-

malities described. If it returned as squamous cell

carcinoma, I would proceed with a full, modified

neck dissection. Otherwise, I would proceed with

excision of the carotid body tumor. If I were in-

formed intraoperatively of paraganglioma cells

being present in the nodes, I would complete a

selective neck dissection encompassing levels

II–IV. However, it is not my normal practice in

the course of carotid body tumor surgery to send

lymph nodes for frozen section analysis unless

they are clearly abnormal. As described in the

answer to Question 6, I send the immediate peri-

carotid bulb lymph nodes, if present, for perma-

nent section analysis.

The likelihood of having to sacrifice the internal

carotid artery in this case would be very low given

the small size of the lesion. However, it is my

practice to have a vascular surgeon on standby in

some fashion for all carotid body tumors for

medicolegal purposes and in case of the unantici-

pated need for vascular bypass and saphenous vein

grafting. I do not routinely have the vascular

surgeon present in the room during the case.

Dr. Carroll: The natural history of these tumors

is often slow, steady growth. A recent publication2

from The Netherlands estimated the tumor-

doubling time at 4.2 years. This slow growth rate

certainly allows time to weigh options. A rushed

decision for surgical resection is rarely needed. In

the index case, the patient is 38 years old with a

small tumor and no documented cranial nerve

deficit. There are no multifocal lesions. We would

usually recommend surgical therapy—particu-

larly in the case when the neck will be violated

for a node biopsy. A wait-and-watch approach with

repeat scanning on a yearly basis is not unreason-

able, and we give patients this option. We are

careful to explain that these tumors typically grow

slowly over time and gradually become more

difficult to remove without accompanying cranial

nerve damage. Collateral cerebral profusion may

diminish with age as well, making risk of carotid

occlusion for significant. The option of primary

radiation is discussed as well. Our preference is to

reserve radiation for very large lesions and for

those who are elderly or infirm.

We approach carotid body tumors in a multi-

disciplinary fashion. The neuroradiologist is in-

volved, as discussed above. The Vascular Surgery

service is also involved in all cases. For small

tumors, the vascular surgeons may simply be on

stand-by status and are called if needed. For large

tumors with a high likelihood of carotid resection,

the vascular surgeons arrange their surgery

schedules to be immediately available. This team

approach allows aggressive and complete resection

of large tumors with a reasonable margin of safety

for the patients.

The patient underwent nasal endoscopy with

biopsy of the nasopharyngeal soft tissue revealing

acute and chronic inflammation of lymphoid tis-

sue. She then underwent neck exploration with

excision of left level IIa and IIIa nodes, which

showed no evidence of lymphoma or other malig-

nancy. Her carotid body tumor was then removed

uneventfully, with the plane of dissection readily

established just deep to the loose carotid adven-

titia. Her postoperative course was uncompli-

cated. One week after surgery, the final pathologic

analysis revealed that the neck mass was consist-

ent with paraganglioma, but there was a micro-

scopic focus of paraganglioma cells in an excised

lymph node.


Question 6: Would you recommend any other

additional treatment for her malignant carotid

body tumor?

Dr. Stenson: The principles of carotid body

tumor resection include early operative manage-

ment, adequate lymph node sampling, and com-

plete tumor resection. These techniques apply to

both benign and malignant carotid body tumors.

Carotid body tumors are known to be slow growing

and generally thought of as radioresistant. One

might consider postoperative radiotherapy for a

large malignant tumor with positive margins and

several positive lymph nodes. If, however, as in

this young patient’s case, there is only one positive

node, the surgeon should consider complete neck

dissection and/or close observation without adju-

vant postoperative therapy. In either situation,

routine follow-up CT may help detect subclini-

cal recurrences that will facilitate timely opera-

tive management.

Dr. Stringer: Absent an extremely aggressive

appearance of the tumor or abnormally enlarged

nodes, the role of routine intraoperative nodal

sampling is not established. It is difficult to obtain

necessary data owing to the rarity of carotid body

tumors and the even more rare incidence of

malignancy. Therefore, we do not know the true

incidence of paraganglioma cells being inciden-

tally present in lymph nodes with a relatively

normal appearance. It is my usual practice to

excise all lymph nodes encountered in the imme-

diate region of the carotid body tumor for perma-

nent histopathologic analysis. As in the present

case, frozen section analysis is not always diag-

nostic of the presence of paraganglioma cells in the

lymph nodes.

I would recommend moderate-dose radiation

therapy postoperatively and reserve neck dissec-

tion for a treatment failure. As discussed above, I

would perform a selective neck dissection only if I

knew of the diagnosis of a malignant lesion

intraoperatively, but I do not think the morbidity

of a secondary neck dissection 1 week later is

justified given our limited knowledge of the benefit

of neck dissection for these tumors and given the

success of moderate-dose radiation in stopping the

growth of paragangliomas.

Dr. Carroll: Malignancy in carotid body tumors

is rare. There are no distinguishing histologic

features of malignancy, and the diagnosis is

confirmed only by finding the tumor in adjacent

lymph nodes or distant sites. For documented me-

tastases in regional nodes with no evidence of

systemic spread, node dissection with postopera-

tive radiation is reasonable. I am aware of no defi-

nitive studies supporting this position.

COMMENTARY

The clinical presentation of this patient is similar

to many patients seen in a general otolaryngology

practice, but the salient features of this history

and physical examination that warrant formula-

tion of a careful differential diagnosis and evalua-

tion are outlined by Dr. Carroll in Question 1. All

of the consultants outline the important diagnostic

considerations, which highlights a key pitfall to

avoid: theCT findingof a carotidbody tumor should

not distract one from considering other pathologic

processes in cases inwhich the clinical picture does

not ‘‘fit’’ the typical presentation of a carotid body

tumor, because more than 90% of carotid body

tumors are benign and slow growing and its treat-

ment may be deferred. As stated by Dr. Stringer,

the most likely etiology of the nasopharyngeal

mass and serous otitis in this patient was adenoi-

ditis, and a trial of antibiotics can be safely given.

When there was incomplete resolution of the

nasopharyngeal abnormality and lymphadenop-

athy, all of the consultants recommended naso-

pharyngeal biopsy either in the clinic or under

general anesthesia. The importance of sampling

lymph nodes to exclude lymphoma is noted by Drs.

Carroll and Stringer. Once the possibility of a con-

current malignancy is ruled out, the carotid body

tumor can be addressed.

Appropriate preoperative evaluation of a car-

otid body tumor centers around three issues:

(1) screening for multiple paragangliomas, (2)

imaging of the cerebral circulation, and (3) use of

preoperative embolization. The 24-h urine screen-

ing for VMAandmetanephrine is recommended by

Drs. Carroll and Stenson but not by Dr. Stringer.

Because the incidence of vasoactive carotid body

tumors is low, this may not be necessary in the

absence of hypertension, tachycardia, and flush-

ing. MRI is the diagnostic study of choice, both for

establishing the diagnosis of carotid body tumor

and for screening for multiple paragangliomas.

Screening MRI is performed routinely by Dr.

Carroll, but Dr. Stringer recommends this only in

case of a positive family history of paragangliomas.

The consultants’ approaches to imaging the ce-

rebral circulation and test occlusion of the carotid

artery are widely divergent. Preoperative carotid

blood flow analysis is no longer used by Dr. Stri-

nger, regardless of size of the tumor, because he

believes test occlusion is not a reliable predictor of


stroke. Dr. Stenson uses test balloon occlusion

with EEG monitoring if the carotid body tumor is

large and partially or completely surrounds the

carotid artery. Dr. Carroll uses balloon occlusion

and SPECT imaging of the cerebral perfusion in all

patients and outlines his rationale for obtaining

this information, which he believes is valuable.

While this area remains controversial, preopera-

tive cerebral perfusion testing is warranted in the

unusual patient with large tumors, in which case

obtaining distal control of, or sewing a graft to, the

internal carotid artery near the skull base may

be difficult.

Preoperative embolization is performed by Dr.

Stenson 1–3 days before surgery in all patients

and by Dr. Carroll the day before surgery in all

patients except those with small tumors. This

again is controversial, since preoperative emboli-

zation can cause inflammation, whichmay obscure

the surgical plane of dissection. It is possible to

resect these tumors with minimal blood loss

without embolization by first circumferentially

ligating and dividing all feeding vessels to the

tumor prior to dissection off the carotid artery. The

only vessel that is difficult to control because it is

usually not accessible until the end of the dis-

section is a small artery that routinely arises from

the posterior aspect of the carotid bulb and enters

the base of the tumor near its attachment to the

carotid bifurcation.

All of the consultants agree that this tumor

should be surgically treated because of the pa-

tient’s young age, small tumor, and natural his-

tory of slow, progressive growth (doubling time of

4.2 years, as noted by Dr. Carroll). There is

unanimity in the need for having vascular sur-

gery colleagues available and/or present if there

is a high likelihood of carotid sacrifice. In this

patient, excisional biopsy of level II and III lymph

nodes to rule out lymphoma is also planned by

the consultants.

The finding of paraganglioma cells with sur-

rounding lymph nodes is one of the hallmarks for

malignant carotid body tumor. Unfortunately, this

was seen only on permanent, not frozen, sections;

this leaves a dilemma as to appropriate additional

treatment. The consultants all recognize that

there is very little information in the medical

literature to strongly support a particular ap-

proach. Dr. Stenson suggests completion neck dis-

section or close observation with serial CT scans,

Dr. Stringer recommends postoperative radiation

therapy, whereas Dr. Carroll suggests neck dis-

section with postoperative radiation.

This patient illustrates many of the nuances

and unanswered questions that arise in the

management of carotid body tumors. Careful

review of the clinical experience by institutions

with large cohorts of patients with this entity may

help address some of these questions.

REFERENCES

1. Shamblin WR, ReMine WH, Sheps SG, Harrison EG.Carotid body tumor (chemodectoma): clinicopathologicanalysis of ninety cases. Am J Surg 1971;122:732–739.

2. Jansen JC, van den Berg R, Kuiper A, van der Mey AG,Zwinderman AH, Cornelisse CJ. Estimation of growth ratein patients with head and neck paragangliomas influencesthe treatment proposal. Cancer 2000;88:2811–2816.


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Malignant carotid body tumor